Parts of this chapter are reproduced or adapted from Caldwell et al.1 © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/. The text below includes substantial additions and formatting changes to the original text, as well as changes to the reporting approach.
In this chapter, we report the systematic review and NMA results for studies reporting an anxiety outcome only. Studies reporting a depression outcome are reported in Chapter 5 and additional and secondary outcomes are reported in Chapter 6.
Systematic review results
Studies included in the review
The overall Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram for the whole review is reported in Figure 2. A total of 11,990 citations were screened, and 1512 full-text articles were retrieved for further screening. Of these, 142 studies were identified as eligible for inclusion in either the anxiety, depression or conduct disorder reviews. Fifty-four studies reported both an anxiety and a depression outcome. The full list of included studies can be found in Appendix 2.
FIGURE 2 Study selection process: PRISMA flow diagram for whole systematic review. a, Not mutually exclusive. Some studies reported both anxiety and depression outcomes. Of 142 studies, 54 reported both anxiety and depression outcomes. Seven did not report either. Forty-eight of 109 studies contributing to the NMA reported both an anxiety and a depression outcome. b, Study was included in the NMA at any of the follow-up time points. Note that references to the main study publication and articles awaiting classification are listed in Appendix 2. (Figure not reproduced here; see the original article.)
Of the 142 studies eligible for the review, 79 included a self-reported anxiety outcome; the details are reported in this chapter. Studies reporting a depression or conduct disorder outcome are reported separately in Chapters 5 and 7. Among the studies reporting an anxiety outcome, the primary focus of 38 studies was the prevention of anxiety whereas 13 were focused on the prevention of depression and 28 addressed both anxiety and depression. Subgroup analyses examining whether or not intervention effects differed by intended focus of the intervention are reported in Exploring heterogeneity and small-study effects.
Study characteristics are reported in Appendix 2. Included studies were published between 1982 and 2018, and randomised between 22 and 5030 participants (median 184 participants). There were 43 cluster randomised studies, of which four reported cluster-adjusted means and SDs and 35 reported model-based estimates. Thirty-six were individually randomised trials. Seventy-three studies reported a post-intervention end point, 38 reported a follow-up of between 6 and 12 months and seven reported a follow-up of between 13 and 24 months. Studies could report more than one follow-up time point; details of studies reporting multiple time points are in Appendix 2.
Forty-four studies were classified as universal and 35 were classified as targeted (27 indicated, eight selective). Twenty-seven studies were implemented in primary schools, 45 in secondary schools, five in tertiary education and two across multiple settings (i.e. two or more settings). Seventy studies were conducted in HICs, with eight conducted in MICs and one in a LIC. Of the studies conducted in HICs, five were conducted in lower-income settings, as specified by the trial authors. Categorisation of LICs and MICs was based on 2017 World Bank classifications.62
Risk-of-bias assessment
Study-level risk-of-bias assessments are reported in Appendix 2. Thirteen of the 79 studies reporting an anxiety outcome were assessed as being at low risk of bias for both random sequence generation and allocation concealment. A further 13 studies reported a suitable randomisation approach, but did not report sufficient details of allocation concealment to allow assessment (i.e. unclear). Fifty studies were judged as having unclear risk of bias for both random sequence generation and allocation concealment. Two studies were judged to have an unclear risk of bias for randomisation and a low risk of bias for allocation concealment. One study was judged to have a low risk of bias for randomisation and a high risk of bias for allocation concealment.
Seventy-three studies were judged to be at high or unclear risk of bias for participant blinding. The six studies judged to have a low risk of bias for participant blinding used active controls or alternative interventions. Study protocols and/or trial registrations were available for 23 studies, of which 20 were considered to have a low risk of bias, and three an unclear risk of bias, for selective outcome reporting. For cluster randomised trials, we also considered how recruitment, randomisation and analysis were conducted under the Cochrane Risk of Bias tool heading of ‘other bias’. Of 43 cluster RCTs, 19 were judged to be at high risk for ‘other bias’.
Interventions and components identified in the review
Table 2 reports the interventions and components identified for studies reporting a self-reported anxiety outcome. Seventeen studies compared three or more interventions. Sixty-two studies included an intervention based on CBT, eight included a relaxation/mindfulness-based intervention, one included an intervention based on CBT + IPT, three included a ‘third-wave’ intervention, four used methods of biofeedback, two included an exercise intervention and two used CBM approaches. One study used an occupational therapy-based intervention. With regard to non-active comparators, 27 studies were waiting list controlled, 17 were ‘usual curriculum’ controlled, 16 had a no-intervention control and 14 used an attention control.
| Study | Focusa | Classification | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Intervention level | Component level, for active intervention only | |||||||||||||
| Armb 1 | Armb 2 | Armb 3 | Armb 4 | Psychoeducation | Cognitive | Behavioural | Mindfulness | Third wave | Relaxation | Physiological | Exercise | BM | ||
| Universal secondary setting | ||||||||||||||
| Araya et al.118 2013 | Depression | (Usual curriculum) | CBT | – | + | + | – | – | – | – | – | – | ||
| Aune and Stiles119 2009 | Anxiety | (No intervention) | CBT | + | + | + | – | – | – | – | – | – | ||
| Baker and Butler120 1984 | Anxiety | CBT | CBT | – | + | + | – | – | + | – | – | – | ||
| – | + | + | – | – | + | – | – | – | ||||||
| Barrett et al.121 2005 | Anxiety | (No intervention) | CBT | + | + | + | – | – | + | – | – | – | ||
| Bonhauser et al.122 2005 | Anxiety + depression | Exercise | Exercise | – | – | – | – | – | – | – | + | – | ||
| Bonhauser et al.122 2005 | – | – | – | – | – | – | – | + | – | |||||
| Britton et al.123 2014 | Anxiety + depression | (Attention control) | Mindfulness/relaxation | – | – | – | + | – | + | – | – | – | ||
| Burckhardt et al.124 2015 | Anxiety + depression | (Attention control) | Mindfulness/relaxation | – | – | – | – | – | + | – | – | – | ||
| Calear et al.125 2009 | Anxiety + depression | (Waiting list) | CBT | – | + | + | – | – | + | – | – | – | ||
| Calear et al.126 2016 | Anxiety | (Waiting list) | CBT | CBT | + | + | + | + | – | + | – | – | – | |
| + | + | + | + | – | + | – | – | – | ||||||
| Calear et al.127 2016 | Anxiety | (Waiting list) | CBT | + | + | + | + | – | + | – | – | – | ||
| Gillham et al.128 2006 | Anxiety + depression | (No intervention) | CBT | + | + | + | – | – | – | – | – | – | ||
| Gucht et al.129 2017 | Anxiety + depression | (Usual curriculum) | Third wave | + | – | – | – | + | – | – | – | – | ||
| Hiebert et al.130 1989 | Anxiety | (Attention control) | Mindfulness/relaxation | + | – | – | – | – | + | + | – | – | ||
| Hodas131 2016 | Anxiety + depression | (Waiting list) | CBT | + | + | + | – | – | – | – | – | – | ||
| Johnson et al.132 2016 | Anxiety + depression | (Usual curriculum) | Third wave | – | – | – | + | + | + | – | – | – | ||
| Johnson et al.133 2017 | Anxiety + depression | (Usual curriculum) | Third wave | Third wave | – | – | – | + | + | + | – | – | – | |
| Johnson et al.133 2017 | – | – | – | + | + | + | – | – | – | |||||
| Lock and Barrett134 2003 | Anxiety | (No intervention) | CBT | + | + | + | – | – | + | – | – | – | ||
| Lowry-Webster et al.135 2001 | Anxiety + depression | (Waiting list) | CBT | + | + | + | – | – | + | – | – | – | ||
| Perry et al.136 2017 | Depression | (Attention control) | CBT | + | + | + | – | – | + | – | – | – | ||
| Potek137 2012 | Anxiety | (Waiting list) | Mindfulness/relaxation | + | – | – | + | – | + | – | – | – | ||
| Roberts et al.138 2003 | Depression | (Usual curriculum) | CBT | – | + | + | – | – | – | – | – | – | ||
| Roberts et al.139 2010 | Anxiety + depression | (Usual curriculum) | CBT | – | + | + | – | – | – | – | – | – | ||
| Rodgers and Dunsmuir140 2015 | Anxiety | (Waiting list) | CBT | + | + | + | – | – | + | – | – | – | ||
| Sheffield et al.141 2006 | Depression | (No intervention) | CBT | + | + | + | – | – | – | – | – | – | ||
| Stallard et al.142 2013 | Depression | (Usual curriculum) | (Attention control) | CBT + IPT | + | + | + | – | – | + | – | – | – | |
| Tomba et al.143 2010 | Anxiety + depression | CBT | CBT | + | + | + | – | – | + | – | – | – | ||
| Tomba et al.143 2010 | + | + | + | – | – | + | – | – | – | |||||
| Wong et al.144 2014 | Anxiety + depression | (Usual curriculum) | CBT | CBT | + | + | + | – | – | – | – | – | – | |
| Wong et al.144 2014 | + | + | + | – | – | – | – | – | – | |||||
| Universal primary setting | ||||||||||||||
| Ahlen et al.145 2018 | Anxiety + depression | (Usual curriculum) | CBT | + | + | + | – | – | + | – | – | – | ||
| Attwood et al.146 2012 | Anxiety | (Attention control) | CBT | + | + | + | – | – | – | – | – | – | ||
| Barrett and Turner147 2001 | Anxiety | (Usual curriculum) | CBT | CBT | + | + | + | – | – | + | – | – | – | |
| Barrett and Turner147 2001 | + | + | + | – | – | + | – | – | – | |||||
| Bouchard et al.148 2013 | Anxiety | (Waiting list) | CBT | + | + | + | – | – | – | – | – | – | ||
| Collins et al.149 2014 | Anxiety | (Usual curriculum) | CBT | CBT | + | + | + | – | – | + | – | – | – | |
| Collins et al.149 2014 | + | + | + | – | – | + | – | – | – | |||||
| Essau et al.150 2012 | Anxiety | (Waiting list) | CBT | + | + | + | – | – | + | – | – | – | ||
| Gallegos151 2008 | Anxiety + depression | (Usual curriculum) | CBT | + | + | + | – | – | + | – | – | – | ||
| Johnstone et al.152 2014 | Anxiety + depression | (Usual curriculum) | CBT | – | + | + | – | – | + | – | – | – | ||
| Miller et al.153 2010 | Anxiety | (Waiting list) | CBT | + | + | + | – | – | – | – | – | – | ||
| Miller et al.154 2011 | Anxiety | (Waiting list) | CBT | + | + | + | – | – | + | – | – | – | ||
| Miller et al.154 2011 | Anxiety | (Attention control) | CBT | + | + | + | – | – | + | – | – | – | ||
| Pattison and Lynd-Stevenson155 2001 | Depression | (No intervention) | (Attention control) | CBT | CBT | – | + | + | – | – | – | – | – | – |
| Pattison and Lynd-Stevenson155 2001 | – | + | + | – | – | – | – | – | – | |||||
| Pophillat et al.156 2016 | Anxiety + depression | (Usual curriculum) | CBT | + | + | – | – | – | – | – | – | – | ||
| Rooney et al.157 2006 | Depression | (No intervention) | CBT | – | + | + | – | – | + | – | – | – | ||
| Ruttledge et al.158 2016 | Anxiety | (Waiting list) | CBT | + | + | + | – | – | + | – | – | – | ||
| Stallard et al.159 2014 | Anxiety | (Usual curriculum) | CBT | CBT | + | + | + | – | – | + | – | – | – | |
| Stallard et al.159 2014 | + | + | + | – | – | + | – | – | – | |||||
| Targeted secondary setting | ||||||||||||||
| Balle and Tortella-Feliu160 2010 | Anxiety | (Waiting list) | CBT | + | + | + | – | – | + | – | – | – | ||
| Berry and Hunt161 2009 | Anxiety | (Waiting list) | CBT | + | + | + | – | – | – | – | – | – | ||
| Cova et al.162 2011 | Depression | (No intervention) | CBT | + | + | + | – | – | – | – | – | – | ||
| Dobson et al.163 2010 | Anxiety + depression | (Attention control) | CBT | – | + | + | – | – | – | – | – | – | ||
| Fitzgerald et al.114 2016 | Anxiety | (Attention control) | CBM | – | – | – | – | – | – | – | – | + | ||
| Gaete et al.164 2016 | Depression | (Usual curriculum) | CBT | – | + | + | – | – | – | – | – | – | ||
| Gillham et al.165 2012 | Depression | (No intervention) | CBT | CBT | + | + | + | – | – | + | – | – | – | |
| Gillham et al.165 2012 | + | + | + | – | – | + | – | – | – | |||||
| Hiebert et al.130 1989 | Anxiety | (Waiting list) | Mindfulness/relaxation | Biofeedback | + | – | – | – | – | + | + | – | – | |
| Hiebert et al.130 1989 | – | – | – | – | – | – | + | – | – | |||||
| Hunt et al.166 2009 | Anxiety | (No intervention) | CBT | + | + | + | – | – | + | – | – | – | ||
| Jordans et al.167 2010 | Anxiety + depression | (Waiting list) | CBT | + | + | + | – | – | – | – | – | – | ||
| Kiselica et al.168 1994 | Anxiety | Psychosupport | CBT | + | + | + | – | – | + | – | – | – | ||
| Owen and Lanning169 1982 | Anxiety | (Waiting list) | Mindfulness/relaxation | CBT | CBT | – | – | – | – | – | + | – | – | – |
| Owen and Lanning169 1982 | + | + | – | – | – | – | – | – | – | |||||
| Owen and Lanning169 1982 | + | + | – | – | – | + | – | – | – | |||||
| Peng et al.170 2015 | Anxiety + depression | (No intervention) | Exercise | – | – | – | – | – | + | – | + | – | ||
| Rice171 2009 | Anxiety | (Attention control) | CBT | Mindfulness/relaxation | + | + | + | – | – | + | – | – | – | |
| Rice171 2009 | – | – | – | – | – | + | – | + | – | |||||
| Scholten et al.172 2016 | Anxiety | (Attention control) | Biofeedback | – | – | – | – | – | + | + | – | – | ||
| Sheffield et al.141 2006 | Depression | (No intervention) | CBT | CBT | CBT | + | + | + | – | – | – | – | – | – |
| Sheffield et al.141 2006 | + | + | + | – | – | – | – | – | – | |||||
| Sheffield et al.141 2006 | + | + | + | – | – | – | – | – | – | |||||
| Sportel et al.117 2013 | Anxiety | (No intervention) | CBM | CBT | – | + | – | – | – | – | – | – | + | |
| Sportel et al.117 2013 | – | + | + | – | – | – | – | – | – | |||||
| Topper et al.173 2017 | Anxiety + depression | (Waiting list) | CBT | + | + | + | – | – | – | – | – | – | ||
| Targeted primary setting | ||||||||||||||
| Cooley-Strickland et al.174 2011 | Anxiety | (Waiting list) | CBT | + | + | + | – | – | + | – | – | – | ||
| Manassis et al.175 2010 | Anxiety + depression | (Attention control) | CBT | + | + | – | – | – | – | – | – | – | ||
| McLoone et al.176 2012 | Anxiety | (Waiting list) | CBT | CBT | + | + | + | – | – | – | – | – | – | |
| McLoone et al.176 2012 | + | + | + | – | – | – | – | – | – | |||||
| Mifsud and Rapee177 2005 | Anxiety | (Waiting list) | CBT | + | + | + | – | – | – | – | – | – | ||
| Miller et al.178 2011 | Anxiety | (Attention control) | CBT | + | + | + | – | – | + | – | – | – | ||
| Schoneveld et al.115 2016 | Anxiety | (Attention control) | Biofeedback | – | – | + | – | – | + | + | – | + | ||
| Schoneveld et al.116 2018 | Anxiety | CBT | Biofeedback | – | + | + | – | – | + | – | – | – | ||
| Schoneveld et al.116 2018 | – | – | + | – | – | – | + | – | + | |||||
| Simpson179 2008 | Anxiety + depression | (Attention control) | CBT | + | + | + | – | – | – | – | – | – | ||
| Siu180 2007 | Anxiety + depression | (Waiting list) | CBT | + | + | + | – | – | + | – | – | – | ||
| Tokolahi et al.181 2018 | Anxiety + depression | (Waiting list) | Occupational therapy | – | – | – | – | – | – | – | – | – | ||
| van Starrenburg et al.182 2017 | Anxiety | (Waiting list) | CBT | + | + | + | – | – | + | – | – | – | ||
| Targeted tertiary/university setting | ||||||||||||||
| Cui et al.183 2016 | Depression | (Waiting list) | Psychosupport | CBT | + | + | + | – | – | + | – | – | – | |
| Ellis et al.184 2011 | Depression | (No intervention) | Psychosupport | CBT | + | + | + | – | – | + | – | – | – | |
| Higgins185 2007 | Anxiety | (No intervention) | CBT | + | + | + | – | – | + | – | – | – | ||
| Seligman et al.186 1999 | Anxiety + depression | (No intervention) | CBT | + | + | + | – | – | + | – | – | – | ||
| Seligman et al.187 2007 | Anxiety + depression | (No intervention) | CBT | + | + | + | – | – | + | – | – | – | ||
| Multiple/mixed settings | ||||||||||||||
| Liddle and Macmillan188 2010 | Anxiety | (Waiting list) | CBT | + | + | + | – | – | + | – | – | – | ||
| Velásquez et al.189 2015 | Anxiety + depression | (Waiting list) | Mindfulness/relaxation | – | – | – | – | – | + | – | – | – | ||
Table 2 also reports the combinations of components identified across all studies reporting an anxiety outcome (at any time point) by population and setting. Components are reported by intervention arm level, and not at the trial level. When there are multiarm trials (i.e. three or more arms) with multiple ‘active’ interventions, intervention components are reported on separate lines. There were 99 active intervention arms, of which 67 had a psychoeducation component. Seventy-eight interventions had a cognitive component, 75 had a behavioural component, eight had a mindful component, four had third-wave components, 60 had a relaxation component, six had a physiological component, four arms had an exercise component and four had a bias modification component.
Further intervention process and delivery characteristics are reported in Appendix 2. The number of sessions implemented ranged from 2 to 120 [mean 11.13 (SD 13.44) sessions]. As a proxy for intervention dose, we calculated the intervention intensity as total session time (number of sessions × duration in minutes). This ranged from 135 to 10,800 minutes [mean 740.15 (SD 1295.60) minutes]. A total of 90% of interventions were delivered to whole classrooms or small groups. Forty-three per cent of interventions were delivered by a MHP, school counsellor or student psychologist, and 10% were delivered by miscellaneous external professionals. Twenty-two per cent of studies used interventions delivered by teachers. Fifteen per cent of studies involved a combination of both teaching and a MHP/psychology professional. Four studies implemented interventions via computer. Two studies could not be classified.
Network meta-analysis results
Of the 79 studies reporting an anxiety outcome, 71 (n = 33,377 participants) contributed data to the NMA for anxiety (across all settings and time points). Forty-eight of these studies also reported a depression outcome and contributed to the depression NMA reported in Chapter 5. The network plot for all studies reporting an anxiety outcome across all populations and settings is reported in Figure 3.
FIGURE 3 Network plot of all eligible studies reporting an anxiety outcome. OT, occupational therapy; third wave, third-wave CBT-based therapies. The plot edges (lines) connecting each pair of interventions represent a direct comparison and are proportional to the number of trials making that direct comparison. Intervention ‘nodes’ are proportional to the number of participants randomised to each intervention. (Figure not reproduced here; see the original article.)
Analyses were conducted separately by population, setting and follow-up time point. Three models were compared for each analysis: a main effects (intervention-level) model, an additive component model and a full interaction component model for the primary time point of immediately post intervention. The longer-term follow-ups of 6–12, 13–24 and ≥ 25 months are reported for the standard intervention-level NMAs only. When data were available from head-to-head trials, we conducted pairwise meta-analyses. The results are reported alongside NMA results in Table 3. Full NMA and pairwise results are reported in Appendix 4.
| Setting | Intervention | Reference intervention | NMA | Direct meta-analysis | Number of direct trials | ||
|---|---|---|---|---|---|---|---|
| SMD | 95% CrI | SMD | 95% CrI | ||||
| Universal secondary | CBT | Usual curriculum | –0.15 | –0.34 to 0.04 | –0.15 | –0.33 to 0.02 | 3 |
| Third wave | Usual curriculum | 0.03 | –0.14 to 0.20 | 0.04 | –0.10 to 0.19 | 3 | |
| Mindfulness/relaxation | Usual curriculum | –0.65 | –1.14 to –0.19 | NA | NA | 0 | |
| Universal primary | CBT | Usual curriculum | –0.07 | –0.23 to 0.05 | –0.08 | –0.24 to 0.04 | 6 |
| Targeted secondary | CBT | No intervention | 0.03 | –0.11 to 0.16 | 0.03 | –0.10 to 0.16 | 4 |
| CBM | No intervention | –0.17 | –0.45 to 0.11 | –0.21 | –0.54 to 0.15 | 1 | |
| Exercise | No intervention | –0.47 | –0.86 to –0.09 | –0.47 | –0.86 to –0.08 | 1 | |
| Biofeedback | No intervention | –0.18 | –0.55 to 0.21 | NA | NA | 0 | |
| Mindfulness/relaxation | No intervention | 0.03 | –0.42 to 0.48 | NA | NA | 0 | |
| Targeted primary | CBT | Waiting list | –0.38 | –0.84 to 0.07 | –0.35 | –0.79 to 0.09 | 5 |
| Occupational therapy | Waiting list | 0.11 | –0.91 to 1.14 | 0.11 | –0.93 to 1.16 | 1 | |
| Biofeedback | Waiting list | –0.38 | –1.50 to 0.72 | NA | NA | 0 | |
Universal population, secondary setting
Post intervention
The analysis-specific network diagram is reported in Figure 4. Twenty-one studies (n = 10,208 participants) contributed to the analysis for the main time point of immediately post intervention.119,120,125–141,143,144 Most studies in this network were judged to be at unclear risk of bias. The risk of bias was judged to be unclear for 13 studies and low for three studies in both the randomised sequence generation and allocation concealment domains. In four studies, the risk of bias was judged to be low for randomisation but unclear for allocation concealment. In one study, the risk of bias was judged to be unclear for randomisation but low for allocation concealment. Sixteen studies included an intervention based on CBT, three were based on third-wave interventions, and two were mindfulness/relaxation-based interventions; the reference intervention was usual curriculum (see Appendix 2 for details). All reported results are from a random-effects NMA model unless otherwise stated. Model fit and selection statistics suggested that a consistency model was appropriate. Of the three models fitted (intervention, additive and full interaction), the additive model was preferred, suggesting evidence for effect modification by components. All model fit statistics are reported in Appendix 3. Results reported in the following sections are SMDs and 95% CrIs.
FIGURE 4 Network plot for universal population, secondary setting: post-intervention anxiety outcome. (Figure not reproduced here; see the original article.)
Intervention-level model
Between-study posterior median SDs (τ) were indicative of moderate heterogeneity (τ 0.11, 95% CrI 0.02 to 0.22). Table 3 reports SMDs (and 95% CrIs) for each active intervention relative to usual curriculum. There was weak evidence of a modest effect of CBT in preventing symptoms of anxiety post intervention (SMD –0.15, 95% CrI –0.34 to 0.04). Mindfulness/relaxation interventions (SMD –0.65, 95% CrI –1.14 to –0.19) reduced symptoms relative to usual curriculum. However, this finding must be interpreted in the context of the possible small-study effects observed in the funnel plot reported in Appendix 6, Figure 17, and the ratings of unclear risk of bias. Only two small mindfulness/relaxation studies (n = 30,130 and n = 79137 participants) contributed to the network, and both were rated as having an unclear risk of bias for random sequence generation and allocation concealment. There was a lack of evidence for the effect of third-wave interventions (SMD 0.03, 95% CrI –0.14 to 0.20).
Additive model: components nested within intervention
Component-level models were fitted to evaluate whether or not the observed between-study heterogeneity in the intervention model could be explained by differences in intervention components.
We fitted an additive model with components nested within interventions, such that a main intervention effect was estimated, plus an additional effect for the inclusion of a specific component. Results are reported as regression coefficients (β-values and 95% CrIs) describing the increase or decrease in SMD via the addition of each component to each intervention. The coefficients can be interpreted as the additional effect of each specific component over and above the ‘common’ intervention-level effect.
All CBT interventions in the universal secondary network included a cognitive and a behavioural component. We estimated the additional effect of including a psychoeducational, mindfulness or relaxation component to cognitive and behavioural components. The between-study heterogeneity was reduced compared with that of the intervention-level analysis (τ 0.06, 95% CrI 0.00 to 0.21) (see Appendix 3). The effect of any CBT intervention including a psychoeducation component was to reduce the SMD (β –0.39, 95% CrI –0.78 to 0.01). The effect of including a mindfulness component in a CBT intervention was to increase the SMD (β 0.57, 95% CrI 0.08 to 1.03) (i.e. less effective at reducing anxiety). There was no evidence to suggest an effect of adding a relaxation component to CBT (β 0.07, 95% CrI –0.21 to 0.38).
Table 4 reports the SMDs for all specific additive combinations of intervention components. Under the additive component model, it is possible to estimate an effect for all combinations, even in the absence of directly observable trials. Relative to a usual curriculum control, there is some evidence that the combination of cognitive + behavioural + psychoeducation components is effective at reducing anxiety post intervention in universal secondary settings (SMD –0.30, 95% CrI –0.59 to –0.01). There is a lack of evidence for all other combinations.
| Population/setting | Main intervention | Components (within main intervention) | Study arms (n) | Model, SMD (95% CrI) | |
|---|---|---|---|---|---|
| Additive | Full interaction | ||||
| Universal secondary, anxiety | CBT | (Cognitive + behavioural) | 2 | 0.09 (–0.17 to 0.36) | 0.09 (–0.22 to 0.40) |
| (Cognitive + behavioural) + psychoeducation | 6 | –0.30 (–0.59 to –0.01) | –0.30 (–0.62 to 0.02) | ||
| (Cognitive + behavioural) + relaxation | 2 | 0.16 (–0.22 to 0.57) | –31.49 (–144.2 to 90.84) | ||
| (Cognitive + behavioural) + psychoeducation + relaxation | 6 | –0.23 (–0.62 to 0.19) | –0.21 (–0.66 to 0.26) | ||
| (Cognitive + behavioural) + psychoeducation + mindfulness + relaxation | 3 | 0.34 (–0.12 to 0.82) | –31.32 (–144 to 91.01) | ||
| (Cognitive + behavioural) + mindfulness | 0 | 0.66 (–0.02 to 1.31) | – | ||
| (Cognitive + behavioural) + mindfulness + relaxation | 0 | 0.73 (0.03 to 1.45) | – | ||
| (Cognitive + behavioural) + psychoeducation + mindfulness | 0 | 0.27 (–0.10 to 0.64) | – | ||
Full interaction model: components nested within intervention
Under a full interaction model, each different combination of intervention and components is considered as a separate intervention. For example, a CBT intervention with cognitive + behavioural + psychoeducation components is considered to be distinct from CBT with cognitive + behavioural + psychoeducation + relaxation components. However, the power to estimate and detect evidence of interactions is limited by the data available for each distinct combination. For the universal secondary anxiety analysis, there were sufficient data to estimate the effects for CBT-based interventions only, although we note that power was low and convergence was problematic. Model fit statistics suggested that the full interaction model was slightly preferred over the intervention-level model, but that the additive effect model is preferred overall (see Appendix 3). However, for completeness, we also report the full interaction results in Table 4. There was weak evidence that CBT with cognitive + behavioural + psychoeducation components is effective relative to usual curriculum (SMD –0.30, 95% CrI –0.62 to 0.02). The between-study posterior median SD was suggestive of low to moderate heterogeneity (τ 0.09, 95% CrI 0.01 to 0.24). Regression coefficients are reported in Appendix 3, but yielded very imprecise estimates of change in SMD.
Universal, secondary, further time points: intervention-level effects
Full results for the following time points are reported in Appendix 6. Details for studies contributing to each time point are reported in Appendix 2.
Six to 12 months post intervention
Fifteen studies (n = 13,150 participants), comparing seven interventions, were included in the analysis for 6–12 months post intervention.118,125,126,128,129,131,133–136,138,139,141–143 Twelve studies included an intervention based on CBT, one study included a CBT + IPT intervention and two studies included a third-wave intervention. There was no evidence to suggest that any intervention reduced symptoms of anxiety between 6 and 12 months, relative to usual curriculum (CBT: SMD –0.11, 95% CrI –0.34 to 0.11; third wave: SMD –0.05, 95% CrI –0.32 to 0.22; and CBT + IPT: SMD –0.02, 95% CrI –0.42 to 0.36). Between-study heterogeneity was moderate (τ 0.15, 95% CrI 0.06 to 0.37).
Thirteen to 24 months post intervention
Three studies (n = 1077 participants) contributed to the analysis for 13–24 months post intervention, all of which included an intervention based on CBT.136,138,139 There was no evidence to suggest that CBT-based interventions prevented symptoms of anxiety between 13 and 24 months, relative to usual curriculum (SMD –0.01, 95% CrI –2.84 to 2.81).
Twenty-five or more months post intervention
One study (n = 92 participants) reported a follow-up time point of 30 months.139 The SMD for the effect of CBT relative to usual curriculum was –0.23 (95% CrI –0.55 to 0.08). The study was rated as having an unclear risk of bias for random sequence generation and allocation concealment.
Universal population, primary setting
Post intervention
The analysis-specific network diagram for universal primary settings is reported in Figure 5. Fifteen studies from 14 publications (n = 5605 participants) contributed to the analysis for the main time point of immediately post intervention.145–158 Thirteen studies were deemed to have an unclear risk of bias and one study was deemed to have a low risk of bias for both randomised sequence generation and allocation concealment domains. One study was judged to be at unclear risk of bias for randomisation but at low risk of bias for allocation concealment. All studies included an intervention based on CBT. Model fit and selection statistics suggested that a random-effects consistency model was appropriate. Fit was similar across all three models (intervention, additive and full interaction) but indicated that the intervention-level model was preferred (see Appendix 3). Therefore, we report effect estimates from the intervention-level analysis only. Regression coefficients from the additive and full interaction models are reported in Appendix 3.
FIGURE 5 Network plot for universal population, primary setting: post-intervention anxiety outcome. (Figure not reproduced here; see the original article.)
Intervention-level model
Between-study posterior median SDs were indicative of moderate heterogeneity (τ 0.10, 95% CrI 0.01 to 0.26). There was weak evidence of a very small effect of CBT relative to usual curriculum (SMD –0.07, 95% CrI –0.23 to 0.05) (see Table 3).
Universal, primary, further time points: intervention-level effects
Six to 12 months post intervention
Ten studies (n = 4794 participants) contributed to the analysis for 6–12 months post intervention, all of which evaluated a CBT-based intervention.145,149–152,154,155,157,159 Between-study posterior median SDs were indicative of substantial heterogeneity (τ 0.22, 95% CrI 0.08 to 0.45). There was no evidence that CBT reduced symptoms of anxiety at between 6 and 12 months, relative to usual curriculum (SMD –0.11, 95% CrI –0.35 to 0.11) (see Appendix 5).
Thirteen to 24 months post intervention
Three studies (n = 1603 participants) contributed to the analysis for 13–24 months post intervention, all of which included an intervention based on CBT.152,157,159 There was no evidence to suggest that CBT-based interventions prevented symptoms of anxiety at between 13 and 24 months, relative to usual curriculum (SMD 0.00, 95% CrI –0.68 to 0.71; τ 0.13).
Twenty-five or more months post intervention
One study (n = 910 participants) reported a follow-up time point of 30 months.152 This study provided weak evidence of a small effect of CBT relative to usual curriculum (SMD –0.12, 95% CrI –0.26 to 0.02). The study was deemed to be at unclear risk of bias for random sequence generation and allocation concealment.
Targeted population, secondary setting
Post intervention
The analysis-specific network diagram for targeted secondary settings is reported in Figure 6. Fifteen studies (n = 2383 participants) contributed to the analysis for the main time point of immediately post intervention.114,117,130,141,160–163,165,167,168,170–173 Three studies were deemed to be at low risk of bias and seven were deemed to be at unclear risk of bias for randomised sequence generation and allocation concealment. Four studies were deemed to be at low risk of bias for randomised sequence generation and at unclear risk for allocation concealment. Five studies were multiarm and compared multiple active interventions. Twelve studies included an intervention based on CBT, two studies examined biofeedback interventions, two studies included a CBM intervention, two studies included a mindfulness/relaxation intervention and one study evaluated study an exercise intervention. Model fit and selection statistics suggested that a random-effects consistency model was appropriate. Model fit was similar across all three intervention models (main intervention, additive and full interaction) (see Appendix 3). There was no evidence of effect modification by intervention components in targeted secondary settings. The intervention-level model is preferred, and regression coefficients from the additive and full interaction models are reported in Appendix 3.
FIGURE 6 Network plot for targeted population, secondary setting: post-intervention anxiety outcome. (Figure not reproduced here; see the original article.)
Intervention-level effects
There was mild to moderate between-study heterogeneity (τ 0.06, 95% CrI 0.00 to 0.21). Table 3 reports SMDs (and 95% CrIs) for each active intervention, relative to no intervention. There was no evidence of an effect for CBT (SMD 0.03, 95% CrI –0.11 to 0.16), biofeedback (SMD –0.18, 95% CrI –0.55 to 0.21), CBM (SMD –0.17, 95% CrI –0.45 to 0.11) or mindfulness/relaxation (SMD 0.03, 95% CrI –0.42 to 0.48). There was evidence that exercise reduced post-intervention anxiety symptoms, relative to no intervention (SMD –0.47, 95% CrI –0.86 to –0.09). However, exercise was evaluated in only one study, which was judged to be at unclear risk of bias for random sequence generation and allocation concealment.
Targeted, secondary, further time points: intervention-level effects only
Six to 12 months post intervention
Six studies (n = 1284 participants) contributed to the analysis for 6–12 months post intervention, of which all included a CBT-based intervention and one included a CBM intervention (three-arm study).117,141,160,163,165,173 There was evidence of mild to moderate between-study heterogeneity (τ 0.06, 95% CrI 0.00 to 0.25). There was no evidence that either CBT (SMD 0.05, 95% CrI –0.12 to 0.20) or CBM (SMD –0.14, 95% CrI –0.53 to 0.24) reduced anxiety at between 6 and 12 months, relative to no intervention.
Thirteen to 24 months, and ≥ 25 months, post intervention
One study (n = 260 participants),166 deemed to be at unclear risk of bias, provided evidence for a small effect of CBT, relative to no intervention, for the prevention of anxiety between 13 and 24 months’ follow-up (SMD –0.26, 95% CrI –0.52 to –0.01) and at 48 months’ follow-up (SMD –0.39, 95% CrI –0.65 to –0.14).
Targeted population, primary setting
Post intervention
The analysis-specific network diagram for targeted primary settings is reported in Figure 7. Eleven studies (n = 1314) contributed to the analysis for the post-intervention time point.115,116,174–182 Three studies were deemed to be at low risk of bias and six studies were deemed to be at unclear risk of bias for both the randomisation and allocation concealment domains. A further two studies were rated as having an unclear risk of bias for allocation concealment, but a low risk of bias for random sequence generation. One study compared two active interventions. Ten studies included an intervention based on CBT, one examined a biofeedback intervention and one included an occupational therapy intervention. Model fit and selection statistics indicated that a random-effects consistency model was appropriate. Model fit was similar across all three intervention models (main intervention, additive and full interaction), but suggested that the intervention-level model was preferred (see Appendix 3). Regression coefficients from the additive and full interaction models are reported in Appendix 3.
FIGURE 7 Network plot for targeted population, primary setting: post-intervention anxiety outcome. OT, occupational therapy. (Figure not reproduced here; see the original article.)
Intervention-level effects
There was evidence of substantial between-study heterogeneity (τ 0.42, 95% CrI 0.21 to 0.89). Table 3 reports SMDs (95% CrIs) for each intervention relative to a waiting list. There was weak evidence of an effect for CBT (SMD –0.38, 95% CrI –0.84 to 0.07), but a lack of evidence for biofeedback (SMD –0.38, 95% CrI –1.50 to 0.72) or occupational therapy (SMD 0.11, 95% CrI –0.91 to 1.14).
Targeted, primary, further time points: intervention-level effects only
Six to 12 months post intervention
Five studies (n = 713 participants) contributed to the analysis for 6–12 months post intervention, of which five included a CBT-based intervention and one included a biofeedback intervention (one study compared two active interventions).116,175–178 The between-study posterior median SD was indicative of substantial heterogeneity (τ 0.52, 95% CrI 0.15 to 2.51). There was no evidence that either CBT (SMD –0.17, 95% CrI –1.37 to 1.06) or biofeedback (SMD –0.28, 95% CrI –2.49 to 1.93) reduced anxiety symptoms at between 6 and 12 months, relative to a waiting list. No studies reported a follow-up of > 12 months post intervention.
Targeted population, tertiary/university setting
The analysis-specific network diagram is reported in Figure 8. Four studies (n = 743 participants) contributed to the analysis for the main post-intervention time point, of which all included an intervention based on CBT.183,184,186,187 Owing to insufficient data in this network, the component models were not fitted.
FIGURE 8 Network plot for targeted population, tertiary/university setting: post-intervention anxiety outcome. (Figure not reproduced here; see the original article.)
Intervention-level model
Post intervention, and 6–12 and 13–24 months post intervention
Model fit and selection statistics suggested that a random-effects consistency model was reasonable (see Appendix 3). However, the between-study posterior median SDs were indicative of substantial heterogeneity (τ 0.43, 95% CrI 0.05 to 2.24). This was considerably reduced in the unrelated intervention effects model (τ 0.21, 95% CrI 0.01 to 2.68), and may indicate the presence of inconsistency. For this reason, results are not reported. However, this potential inconsistency should be interpreted in the light of the inclusion criteria that interventions needed to be delivered in the educational institution, and the unanticipated limitations this caused for the tertiary/university setting analyses. We consider the limitations in Chapter 10, Limitations relating to inclusion criteria.
Exploring heterogeneity and small-study effects
Subgroup analyses, metaregression and sensitivity analyses were conducted for the intervention-level NMA, for the main outcome and for the primary end point of post intervention only. The comparison-adjusted funnel plots suggest that small study effects are possible in the universal primary and secondary settings analyses. That is, smaller studies may be reporting more beneficial results than larger studies among non-active controlled trials reporting an anxiety outcome (see Appendix 6). This is a potentially important finding. Of all the populations and settings considered in this chapter, the universal analyses provided the strongest evidence for a reduction in anxiety post intervention. There was no evidence to suggest the presence of small-study effects for the analyses of targeted populations in either setting.
A metaregression was conducted for intervention mode of delivery (face to face or via computer), and for intervention facilitator (teacher or a MHP). There was no evidence of effect modification by facilitator or mode of delivery for any population or setting combination (see Appendix 6). However, for the universal primary analysis, there was weak evidence that teacher-delivered CBT interventions (SMD –0.05, 95% CrI –0.21 to 0.08) may be slightly less effective than MHP-delivered CBT interventions (SMD –0.18, 95% CrI –0.42 to 0.00).
Subgroup analyses were conducted to evaluate if intervention effects differed by intended focus of the intervention. For each population and setting combination, intervention estimates were compared across three subgroups: (1) interventions that aimed to prevent anxiety (2) interventions that aimed to prevent only depressive symptoms and (3) interventions that aimed to prevent both anxiety and depression.
For the universal secondary and universal primary anxiety networks, there was very weak evidence that intervention focus was important. Interventions focused on preventing anxiety appeared to have a larger effect on anxiety symptoms than those focusing on depression or combined depression and anxiety. However, CrIs overlapped, and we did not conduct a statistical test to examine subgroup differences. For targeted populations, there was some evidence to suggest that interventions focusing on both anxiety and depression were slightly more effective than interventions focused on anxiety alone. However, we emphasise that these results are to be considered descriptive only. Full results are reported in Appendix 6.
Sensitivity analyses: risk of bias
Sensitivity analyses were conducted for the intervention-level NMA, for the main outcome and primary end point of post intervention only. We explored the robustness of the findings to excluding studies judged to be at high/unclear risk of bias for the domains of random sequence generation and allocation concealment.
Having removed studies judged to be at high/unclear risk of bias, few studies were eligible for inclusion. In the universal secondary network, only three studies125,126,141 of three interventions (waiting list, no intervention and CBT) remained after excluding studies judged to be at high risk of bias, and there was no evidence of an effect for CBT (SMD –0.07, 95% CrI –0.77 to 0.58), relative to a waiting list control (Table 5). For targeted secondary interventions, there were three studies judged to be at low risk of bias comparing four interventions (waiting list, no intervention, CBT and CBM).117,141,167 There was no evidence of a beneficial effect for either CBT (SMD 0.07, 95% CrI –0.25 to 0.41) or CBM (SMD –0.20, 95% CrI –0.69 to 0.30), relative to no intervention. One study was judged to be at low risk of bias in the universal primary network.145 A sensitivity analysis was not possible for the targeted primary network.
| Population/setting | Intervention | Reference intervention | Trials (n) | SMD (95% CrI) | |
|---|---|---|---|---|---|
| Low risk of bias | All | ||||
| Universal secondary | CBT | Waiting list | 3 | –0.07 (–0.77 to 0.58) | –0.09 (–0.24 to 0.03) |
| Universal primary | CBT | Usual curriculum | 1 | –0.01 (–0.18 to 0.17)a | –0.07 (–0.23 to 0.05) |
| Targeted secondary | CBT | No intervention | 3 | 0.07 (–0.25 to 0.41) | 0.03 (–0.11 to 0.16) |
| CBM | No intervention | –0.20 (–0.69 to 0.30) | –0.17 (–0.45 to 0.11) | ||
Sensitivity analyses: intracluster correlation coefficient and change from baseline scores
When cluster randomised trials did not explicitly account for clustering in their analyses, we followed the advice in the Cochrane handbook (section 16.3.4)81 for calculating an approximate sample size, using an ICC of 0.03. We explored the robustness of this decision in a best-case/worst-case sensitivity analysis using ICCs of 0.01 and 0.06, respectively. All results were robust to alternative ICC values. To calculate the standardised mean change from baseline, we assumed a correlation of 0.7, which was based on previous analyses (see Chapter 2, Data preparation). Sensitivity analyses were robust to using correlation values of 0.6 and 0.8 (see Appendix 6).
Summary of main results
Seventy-nine studies met the inclusion criteria for the anxiety prevention review, most of which (n = 66) were deemed to be at high or unclear risk of bias for random sequence generation and/or allocation concealment. In addition, there was evidence of possible small-study effects in the universal primary and universal secondary networks. Moderate levels of heterogeneity were observed in all analyses.
A more detailed interpretation of the results, applying the criteria outlined in Chapter 3, is considered in Chapter 9. Seventy-one studies contributed data to the NMA. In the universal secondary network, there was evidence that mindfulness/relaxation interventions (SMD –0.65, 95% CrI –1.14 to –0.19) reduced symptoms of anxiety, relative to usual curriculum. There was weak evidence for a small effect of CBT in reducing self-reported anxiety symptoms (SMD –0.15, 95% CrI –0.34 to 0.04). However, the two mindfulness/relaxation studies were connected to the network only via single small studies.130,137 Both studies were rated as having an unclear risk of bias for random sequence generation and allocation concealment. The CBT estimate is based on 16 studies (n = 8851 participants),119,120,125–128,131,134–136,138–141,143,144 of which three (n = 4001 participants) were judged to be at low risk of bias for random sequence generation and allocation concealment.125,126,141 This could, therefore, be considered a more robust finding (because of the lower risk of bias).
There was evidence of effect modification by intervention components for the CBT interventions in the universal secondary network. The additive components analysis suggests that a CBT intervention with a psychoeducation component was more effective than other CBT combinations. There was a reduction in the SMD of –0.39 (95% CrI –0.78 to 0.01) for CBT interventions with a psychoeducation component.
Studies included in the universal primary network were mostly judged to be at unclear risk of bias. There was weak evidence of a very small effect that CBT prevented symptoms of anxiety, relative to usual curriculum, at post intervention.
For the targeted secondary analysis there was evidence that exercise was effective, relative to no intervention (SMD –0.47, 95% CrI –0.86 to –0.09). However, this was based on a single study, connected to the network via no intervention (n = 121 participants) and judged to be at unclear risk of selection bias.170 There was no evidence of an effect for any other type of intervention in this network.
There was weak evidence to suggest that CBT was effective, relative to waiting list, in the targeted primary analysis at post intervention.
There was evidence of inconsistency in the targeted tertiary/university network. We consider this, and the limitations imposed by the inclusion criteria on the validity of the university network, in Chapter 10, Limitations relating to inclusion criteria.